Week 2 Protein Degradation Module Flashcards
What is the functional difference between proteins with long life spans and proteins with relatively short lifespans?
Long lived proteins: may be involved with structure of the cell
Short lived proteins: need to respond quickly to change and are likely part of metabolic processes, cell signaling, or cell division
Define Proteolysis
breakdown of proteins into peptide fragments and AAs
Define proteases
the enzymes responsible for the breakdown of proteins
What are the two pathways of protein degradation?
ubiquitin-proteasome pathway, lysosomal pathway
describe the ubiquitin-proteasome pathway: general pathway? what does it degrade? does it require energy?
General pathway: proteins are marked with a chaing of ubiquitin molecules and then degraded by proteasomes
A selective process that degrades short-lived, damaged or misfolded proteins.
Requires ATP
What enzymes are involved in ubiquination of proteins?
E1
E2
E3
At what points is ATP needed for the ubiquitin-proteasome pathway?
ATP is needed to attach Ub to E1. and ATP is needed during the breakdown of proteins with proteasome
Describe how the enzymes work in the ubiquitin-proteasome pathway
Ub attaches to E1 (ATP is hydrolyzed)–>E1-Ub transfers its Ub to E2–>E3 ligase transfers Ub to the target protein
After a Ub tagged protein is degraded, what happens to attacehd Ub?
they are recylced
What is the general structure of a proteasome?
contain an inner active site (protein degradation) and out protein binding sites.
compare the relative number of different E3 and E1 enzymes?
the genome has >600 Ub E3 ligases and much fewer E1 enzymes.
How do cytosolic proteins enter a lysosome?
Autophagy!
What are the three types of Autophagy?
Macroautophagy, microautophagy, chaperone-mediated autophagy
What types of things are consume with macroautophagy? (3)
proteins, protein aggregates, mitochondrium (organelles)
Describe the process/steps of macroautophagy
an isolation membrane (double membrane) expands to engulf cytosolic cargo–>cargo is sequestered in autophagosome (closed isolation membrane)–>autophagosome fuses with lysosome and contents are degraded
Describe the steps of microautophagy
lysosome invaginates and directly eats cytosolic components
What is an autophagic tube? where is it seen?
the invagination of the lysosome seen during the process of microautophagy. Vesicles bud off the tube and into the lysosome.
describe the selectivity of macroautophagy, microautophagy, and chaperone-mediated autophagy
micro and macro: can be random or selective.
Chaperone: highly selective
what types of proteins are degraded by chaperone-mediated autophagy?
long-lived dispensable proteins (contrasts to Ub-mediated that degrades short lived)
what motif targets proteins to chaperone-mediated autophagy?
KFEQR motif
what are the steps of chaperone-mediated autophagy
Protein with KFEQR motif binds chaperone in cytosol–>chaperone targets protein to lysosomal membrane–>protein binds LAMP2A on surface of lysosomal membrane–>LAMP2A translocates protein into lysosomal lumen
what induces autophagy?
cellular stress
In general, what type of proteins are targeted by Ub-proteasome pathway and Autophagy? Selectivity?
Autophagy: long lived proteins and organelles (selective or non-selective)
Ub-Proteasome: short lived, damaged, or misfolded proteins. highly selective
what is mTOR? what does it do? during cell stress?
mTOR is a master regulator that positively promotes cell growth and proliferation. in a healthy cell mTOR inhibits expression of autophagy related genes. Under cellular stress mTOR signaling is impaired and Atgs are upregulated
